Sex differences in functional outcomes of intravenous thrombolysis among patients with lacunar stroke.

Background: This study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS). Methods: Consecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke. Results: A total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th-75th percentiles 67-84 years versus 70 years, 25th-75th percentiles 60-80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01-2.19, value of p 0.044). Conclusion: This study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

Sex Differences in Outcomes of Intravenous Thrombolysis in Acute Ischemic Stroke Patients with Preadmission Use of Antiplatelets.

AIM: To compare safety and functional outcomes of intravenous thrombolysis (IVT) between females and males with acute ischaemic stroke (AIS) in relation to preadmission use of antiplatelets. METHODS: Multicentre cohort study of patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry, presenting with AIS and receiving IVT. Primary safety outcome was in-hospital symptomatic intracerebral haemorrhage (sICH). Primary functional outcome was functional independence at 3 months after discharge. Multivariable logistic regression models were fitted to assess the association between sex and each outcome according to preadmission use of antiplatelets. RESULTS: The study included 4996 patients (42.51 % females, older than males, median age 79 vs 71 years, p < 0.0001). Comparable proportions of females (39.92 %) and males (40.39 %) used antiplatelets before admission (p = 0.74). In total, 3.06 % females and 2.47 % males developed in-hospital sICH (p = 0.19), with similar odds (adjusted odds ratio, [AOR] 0.93, 95 % confidence interval, [CI] 0.63-1.39). No interaction was found between sex and preadmission use of either single or dual antiplatelets in relation to in-hospital sICH (p = 0.94 and p = 0.23). Males had higher odds of functional independence at 3 months (AOR 1.34, 95 % CI 1.09-1.65), regardless of preadmission use of antiplatelets (interaction between sex and preadmission use of either single or dual antiplatelets p = 0.41 and p = 0.58). CONCLUSION: No sex differences were observed in the safety of IVT regarding preadmission use of antiplatelets. Males showed more favourable 3-month functional independence than females; however, this sex difference was apparently not explained by a sex-specific mechanism related to preadmission use of antiplatelets.

Effect of admission time on provision of acute stroke treatment at stroke units and stroke centers-An analysis of the Swiss Stroke Registry.

Introduction: Rapid treatment of acute ischemic stroke (AIS) depends on sufficient staffing which differs between Stroke Centers and Stroke Units in Switzerland. We studied the effect of admission time on performance measures of AIS treatment and related temporal trends over time. Patients and methods: We compared treatment rates, door-to-image-time, door-to-needle-time, and door-to-groin-puncture-time in stroke patients admitted during office hours (Monday-Friday 8:00-17:59) and non-office hours at all certified Stroke Centers and Stroke Units in Switzerland, as well as secular trends thereof between 2014 and 2019, using data from the Swiss Stroke Registry. Secondary outcomes were modified Rankin Scale and mortality at 3 months. Results: Data were eligible for analysis in 31,788 (90.2%) of 35,261 patients. Treatment rates for IVT/EVT were higher during non-office hours compared with office hours in Stroke Centers (40.8 vs 36.5%) and Stroke Units (21.8 vs 18.5%). Door-to-image-time and door-to-needle-time increased significantly during non-office hours. Median (IQR) door-to-groin-puncture-time at Stroke Centers was longer during non-office hours compared to office hours (84 (59-116) vs 95 (66-130) minutes). Admission during non-office hours was independently associated with worse functional outcome (1.11 [95%CI: 1.04-1.18]) and increased mortality (1.13 [95%CI: 1.01-1.27]). From 2014 to 2019, median door-to-groin-puncture-time improved and the treatment rate for wake-up strokes increased. Discussion and Conclusion: Despite differences in staffing, patient admission during non-office hours delayed IVT to a similar, modest degree at Stroke Centers and Stroke Units. A larger delay of EVT was observed during non-office hours, but Stroke Centers sped up delivery of EVT over time. Patients admitted during non-office hours had worse functional outcomes, which was not explained by treatment delays.

Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce. METHODS: We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). RESULTS: We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031). CONCLUSIONS: Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.

Central Retinal Artery Occlusion: Current Practice, Awareness and Prehospital Delays in Switzerland.

Background and Purpose: Central retinal artery occlusion (CRAO) often leads to permanent monocular blindness. Hence, early recognition and rapid re-perfusion is of paramount importance. This study aims to describe prehospital pathways in CRAO compared to stroke and study the knowledge about CRAO. Methods: (1) Description of baseline characteristics, prehospital pathways/delays, and acute treatment (thrombolysis/thrombectomy vs. standard of care) of patients with CRAO and ischemic stroke registered in the Swiss Stroke Registry. (2) Online survey about CRAO knowledge amongst population, general practitioners (GPs) and ophthalmologists in Eastern Switzerland. Results: Three hundred and ninety seven CRAO and 32,816 ischemic stroke cases were registered from 2014 until 2019 in 20 Stroke Centers/Units in Switzerland. In CRAO, 25.6% arrived at the hospital within 4 h of symptom onset and had a lower rate of emergency referrals. Hence, the symptom-to-door time was significantly longer in CRAO compared to stroke (852 min. vs. 300 min). The thrombolysis/thrombectomy rate was 13.2% in CRAO and 30.9% in stroke. 28.6% of the surveyed population recognized CRAO-symptoms, 55.4% of which would present directly to the emergency department in contrast to 90.0% with stroke symptoms. Almost 100% of the ophthalmologist and general practitioners recognized CRAO as a medical emergency and 1/3 of them considered IV thrombolysis a potentially beneficial therapy. Conclusions: CRAO awareness of the general population and physician awareness about the treatment options as well as the non-standardized prehospital organization, seems to be the main reason for the prehospital delays and impedes treating CRAO patients. Educational efforts should be undertaken to improve awareness about CRAO.

Magnetic Resonance Imaging or Computed Tomography for Suspected Acute Stroke: Association of Admission Image Modality with Acute Recanalization Therapies, Workflow Metrics, and Outcomes.

OBJECTIVE: To examine rates of intravenous thrombolysis (IVT), mechanical thrombectomy (MT), door-to-needle (DTN) time, door-to-puncture (DTP) time, and functional outcome between patients with admission magnetic resonance imaging (MRI) versus computed tomography (CT). METHODS: An observational cohort study of consecutive patients using a target trial design within the nationwide Swiss-Stroke-Registry from January 2014 to August 2020 was carried out. Exclusion criteria included MRI contraindications, transferred patients, and unstable or frail patients. Multilevel mixed-effects logistic regression with multiple imputation was used to calculate adjusted odds ratios with 95% confidence intervals for IVT, MT, DTN, DTP, and good functional outcome (mRS 0-2) at 90 days. RESULTS: Of the 11,049 patients included (mean [SD] age, 71 [15] years; 4,811 [44%] women; 69% ischemic stroke, 16% transient ischemic attack, 8% stroke mimics, 6% intracranial hemorrhage), 3,741 (34%) received MRI and 7,308 (66%) CT. Patients undergoing MRI had lower National Institutes of Health Stroke Scale (median [interquartile range] 2 [0-6] vs 4 [1-11]), and presented later after symptom onset (150 vs 123 min, p < 0.001). Admission MRI was associated with: lower adjusted odds of IVT (aOR 0.83, 0.73-0.96), but not with MT (aOR 1.11, 0.93-1.34); longer adjusted DTN (+22 min [13-30]), but not with longer DTP times; and higher adjusted odds of favorable outcome (aOR 1.54, 1.30-1.81). INTERPRETATION: We found an association of MRI with lower rates of IVT and a significant delay in DTN, but not in DTP and rates of MT. Given the delays in workflow metrics, prospective trials are required to show that tissue-based benefits of baseline MRI compensate for the temporal benefits of CT. ANN NEUROL 2022;92:184-194.

Ischemic stroke in COVID-19 patients: Mechanisms, treatment, and outcomes in a consecutive Swiss Stroke Registry analysis.

BACKGROUND: Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to selected centers or lack 3-month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3-month outcomes of patients with IS and COVID-19 in a nationwide stroke registry. METHODS: From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID-19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3-month outcome of SARS-CoV-2 polymerase chain reaction-positive (PCR+) IS patients to SARS-CoV-2 PCR- and/or asymptomatic non-tested IS patients. RESULTS: Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08-5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14-0.99, p = 0.049). COVID-19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS-adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96-3.58, p = 0.07). CONCLUSIONS: In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multi-territory stroke and less often cryptogenic stroke, and their 3-month functional outcome tended to be worse.

Association of the COVID-19 outbreak with acute stroke care in Switzerland.

BACKGROUND AND PURPOSE: In Switzerland, the COVID-19 incidence during the first pandemic wave was high. Our aim was to assess the association of the outbreak with acute stroke care in Switzerland in spring 2020. METHODS: This was a retrospective analysis based on the Swiss Stroke Registry, which includes consecutive patients with acute cerebrovascular events admitted to Swiss Stroke Units and Stroke Centers. A linear model was fitted to the weekly admission from 2018 and 2019 and was used to quantify deviations from the expected weekly admissions from 13 March to 26 April 2020 (the "lockdown period"). Characteristics and 3-month outcome of patients admitted during the lockdown period were compared with patients admitted during the same calendar period of 2018 and 2019. RESULTS: In all, 28,310 patients admitted between 1 January 2018 and 26 April 2020 were included. Of these, 4491 (15.9%) were admitted in the periods March 13-April 26 of the years 2018-2020. During the lockdown in 2020, the weekly admissions dropped by up to 22% compared to rates expected from 2018 and 2019. During three consecutive weeks, weekly admissions fell below the 5% quantile (likelihood 0.38%). The proportion of intracerebral hemorrhage amongst all registered admissions increased from 7.1% to 9.3% (p = 0.006), and numerically less severe strokes were observed (median National Institutes of Health Stroke Scale from 3 to 2, p = 0.07). CONCLUSIONS: Admissions and clinical severity of acute cerebrovascular events decreased substantially during the lockdown in Switzerland. Delivery and quality of acute stroke care were maintained.

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation.

OBJECTIVE: The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes. METHODS: This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months. RESULTS: Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: ß -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51). INTERPRETATION: Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53.

Enhancing Visibility of the Hypopharyngeal-Esophageal Region by Introduction of a Physiological Eructation Maneuver.

BACKGROUND: In routine medical examination, the hypopharyngeal-esophageal area (HER) is difficult to assess due to its position and anatomical complexity. The purpose of this study was to evaluate the feasibility of a volitional eructation maneuver during transnasal flexible laryngoscopy and its influence on the visibility of the HER. METHODS: Twenty healthy volunteers underwent flexible laryngoscopy. Once the larynx was freely visible during laryngoscopy, the subjects were asked to trigger a "burp." The volitional belching during the study was assisted by drinking a carbonated cold drink. The triggered relaxation of the upper esophageal sphincter along with the widening of the hypopharynx region was recorded and subsequently analyzed frame by frame. RESULTS: Out of 20 volunteers, 16 (80%) were able to volitionally induce an eructation. Significant widening of the hypopharynx region up to the relaxant upper esophageal sphincter could be recorded. The structures were clearly visible in the offline analysis. In 13 (81%) of the 16 subjects who could induce an eructation, the upper esophageal sphincter was partially visible or free for full inspection. CONCLUSION: The eructation method as a simple physiological function can be used as a complementary method during flexible transnasal endoscopy to enhance visibility of the entire hypopharynx region as well as the upper esophageal sphincter.

Prevalence, determinants, and effect on quality of life of freezing of gait in Parkinson disease.

IMPORTANCE: Freezing of gait (FOG) is a common axial symptom of Parkinson disease (PD). OBJECTIVE: To determine the prevalence of FOG in a large group of PD patients, assess its relationship with quality of life and clinical and pharmacological factors, and explore its changes from the off to on conditions in patients with motor fluctuations. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey of 683 patients with idiopathic PD. Scores for FOG were missing in 11 patients who were not included in the analysis. Patients were recruited from referral centers and general neurology clinics in public or private institutions in France. EXPOSURE: Patients with FOG were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson's Disease Rating Scale (UPDRS) in the on condition. Item 14 scores for FOG in the off condition were also collected in patients with fluctuating motor symptoms. MAIN OUTCOMES AND MEASURES: Quality of life (measured by the 39-item Parkinson's Disease Questionnaire and 36-Item Short Form Health Survey), anxiety and depression (Hospital Anxiety and Depression Scale), clinical features (UPDRS), and drug consumption. RESULTS: Of 672 PD patients, 257 reported FOG during the onstate (38.2%), which was significantly related to lower quality of life scores (P < .01). Freezing of gait was also correlated with longer PD duration (odds ratio, 1.92 [95% CI, 1.28-2.86]), higher UPDRS parts II and III scores (4.67 [3.21-6.78]), the presence of apathy (UPDRS item 4) (1.94 [1.33-2.82]), a higher levodopa equivalent daily dose (1.63 [1.09-2.43]), and more frequent exposure to antimuscarinics (3.07 [1.35-6.97]) (logistic regression). The FOG score improved from the off to on states in 148 of 174 patients with motor fluctuations (85.1%) and showed no change in 13.8%. The FOG score improved by more than 50% in 43.7% of patients. Greater improvement in the on state was observed in younger patients (r = -0.25; P < .01) with lower UPDRS II and III scores (r = -0.50; P < .01) and no antimuscarinic use (r = -0.21; P < .01). CONCLUSIONS AND RELEVANCE: Freezing of gait in PD patients correlates with poor quality of life, disease severity, apathy, and exposure to antimuscarinics. Dopaminergic therapy improved FOG in most patients with motor fluctuations, especially younger ones with less severe disease and no antimuscarinic use. This finding suggests that quality of life is impaired in PD patients with FOG and that optimizing dopaminergic therapy and avoiding antimuscarinics should be considered.

Early development of spasticity following stroke: a prospective, observational trial.

This study followed a cohort of 103 patients at median 6 days, 6 and 16 weeks after stroke and recorded muscle tone, pain, paresis, Barthel Index and quality of life score (EQ-5D) to identify risk-factors for development of spasticity. 24.5% of stroke victims developed an increase of muscle tone within 2 weeks after stroke. Patients with spasticity had significantly higher incidences of pain and nursing home placement and lower Barthel and EQ-5D scores than patients with normal muscle tone. Early predictive factors for presence of severe spasticity [modified Ashworth scale score (MAS) >or=3] at final follow-up were moderate increase in muscle tone at baseline and/or first follow-up (MAS = 2), low Barthel Index at baseline, hemispasticity, involvement of more than two joints at first follow-up, and paresis at any assessment point. The study helps to identify patients at highest risk for permanent and severe spasticity, and advocates for early treatment in this group.

123I-metaiodobenzylguanidine scintigraphy in Parkinson's disease and related disorders.

Autonomic dysfunction is common in Lewy body disorders (Parkinson's disease, Dementia with Lewy Bodies, Pure Autonomic Failure, and REM sleep disorder). The loss of post-ganglionic myocardial sympathetic nerve fibers is a prominent feature of autonomic dysfunction in such disorders. (123)I-metaiodobenzylguanidine (MIBG) scintigraphy that visualizes catecholaminergic terminals in vivo is a biomarker used to detect cardiac sympathetic degeneration. Abnormal MIBG uptake has been consistently reported in Lewy body disorders. Some studies agree in the notion that increasing bradykinesia is related with an incremental cardiac sympathetic denervation, whereas tremor is not closely linked to cardiac denervation. "Atypical" parkinsonian syndromes, including Multiple System Atrophy, Progressive Supranuclear Palsy, and others, show modest reductions of cardial MIBG uptake. MIBG scintigraphy is moderately sensitive and specific in differentiating Parkinson's disease from such syndromes. Conversely, its sensitivity and specificity might be better in cognitively impaired patients, helping differential diagnosis between Dementia with Lewy Bodies, and Alzheimer disease. Confounding factors (comorbidities, comedications) should be carefully controlled before analyzing MIBG scintigraphy.

Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial.

About 30% of patients with chronic upper motor neuron syndrome (UMNS) suffer from disabling spasticity-related pain not sufficiently correctable by conventional treatment. Delta9-tetrahydrocannabinol (Delta(9)-THC) was reported to add benefit in the treatment of pain in patients with multiple sclerosis (MS). The question arose whether synthetic cannabinoids with lower potential for psychotropic side effects could be effective as well. To evaluate the safety and efficacy of low dose treatment with the synthetic cannabinoid Nabilone (1 mg per day) on spasticity-related pain a placebo-controlled double-blind crossover trial was performed.11 out of 13 included patients completed the study. The 11-Point-Box-Test showed a significant decrease of pain under Nabilone (p < 0.05), while spasticity, motor function and activities of daily living did not change. 5 patients reported side effects: one moderate transient weakness of the lower limbs (Nabilone phase, drop out), three mild drowsiness (two Nabilone, one placebo) and one mild dysphagia (placebo). One patient was excluded from the study due to an acute relapse of multiple sclerosis (Nabilone phase, drop out). Nabilone 1 mg per day proved to be a safe and easily applicable option in the care of patients with chronic UMNS and spasticity-related pain otherwise not controllable.